Abstract
ABSTRACTIntroduction: Noggin is an antagonist of bone morphogenetic proteins (BMPs) and has a strong effect on osteogenesis. Osteoporosis is a common complication of transfusion dependent beta-thalassemia (TDT) and denosumab has been recently emerged as a promising therapeutic option. This was a post hoc investigation of serum noggin levels among TDT patients with osteoporosis who participated in a randomized, placebo-control, phase 2b study.Methods: Patients received either 60 mg denosumab (n = 32) or placebo (n = 31) every 6 months for 12 months. Noggin was measured, for the first time in thalassemia patients, at baseline and at 12 months, using a recently developed high sensitivity fluorescent immunoassay.Results: Both groups showed a significant increase in noggin serum levels (denosumab p < 0.001; placebo p < 0.0001). Interestingly, the increase was higher in the placebo group. Furthermore, we observed a strong correlation between noggin and wrist bone mineral density (r = −0.641, p = 0.002) only in the denosumab group.Conclusion: In conclusion, higher noggin levels reflected more BMP inhibition, since our assay detects free bioactive noggin, which in turn impaired bone formation in placebo group. Therefore, denosumab possibly regulates noggin and favours bone turnover in TDT patients with osteoporosis through a novel mechanism of action.Trial registration: ClinicalTrials.gov identifier: NCT02559648.
Highlights
Noggin is an antagonist of bone morphogenetic proteins (BMPs) and has a strong effect on osteogenesis
We have evaluated the effect of denosumab on transfusion-dependent beta-thalassemia (TDT)-induced osteoporosis and we have found encouraging results pertaining to an improvement in bone mineral density (BMD) and a reduction in pain scores and markers of bone resorption [5]
We observed a significant increase in serum levels of noggin among patients both in the denosumab and the placebo groups; it was more pronounced in the latter group
Summary
Noggin is an antagonist of bone morphogenetic proteins (BMPs) and has a strong effect on osteogenesis. Osteoporosis is a common complication of transfusion dependent betathalassemia (TDT) and denosumab has been recently emerged as a promising therapeutic option. This was a post hoc investigation of serum noggin levels among TDT patients with osteoporosis who participated in a randomized, placebo-control, phase 2b study. Increased levels of RANKL have been identified among thalassemia patients [11] In this context, we have evaluated the effect of denosumab on TDT-induced osteoporosis and we have found encouraging results pertaining to an improvement in BMD and a reduction in pain scores and markers of bone resorption [5]
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